{"title":"MiR-200a-3p Attenuates Neuropathic Pain by Suppressing the Bromodomain-Containing Protein 3-Nuclear Factor-κB Pathway","authors":"Chao Deng, Xuequan Yuan, Xuezheng Lin, Sitong Liu","doi":"10.1002/jbt.70041","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>MicroRNAs (miRNAs) have key roles in the pathological processes of neuropathic pain. Here, our aim was to elucidate the function of miR-200a-3p as well as its related regulatory mechanism in neuropathic pain. An animal model of neuropathic pain was established by chronic constriction injury (CCI) induction. The knockdown experiments are performed by injecting a lentiviral construct intrathecally. MiR-200a-3p and bromodomain-containing protein 3 (BRD3) expression in rat spinal cord was determined using RT-qPCR. The mechanical, thermal, and cold responses in animals were assessed at the indicated time after surgery. The levels of inflammatory cytokines in rat spinal cord were measured by ELISA. The changes in NF-κB signaling-related molecules in rat spinal cord were determined using western blot and immunofluorescence. MiR-200a-3p was underexpressed in CCI rats in a time-dependent manner. Overexpression of miR-200a-3p decreased mechanical hyperalgesia and thermal sensitivity to attenuate neuropathic pain in rats. BRD3 was targeted by miR-200a-3p. Additionally, downregulation of BRD3 inhibited neuropathic pain progression. Moreover, overexpression of BRD3 rescued the effect of miR-200a-3p on NF-κB signaling and neuropathic pain in CCI rats. MiR-200a-3p attenuates neuropathic pain via downregulating BRD3 to block NF-κB signaling.</p>\n </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 12","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70041","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
MiR-200a-3p Attenuates Neuropathic Pain by Suppressing the Bromodomain-Containing Protein 3-Nuclear Factor-κB Pathway
MicroRNAs (miRNAs) have key roles in the pathological processes of neuropathic pain. Here, our aim was to elucidate the function of miR-200a-3p as well as its related regulatory mechanism in neuropathic pain. An animal model of neuropathic pain was established by chronic constriction injury (CCI) induction. The knockdown experiments are performed by injecting a lentiviral construct intrathecally. MiR-200a-3p and bromodomain-containing protein 3 (BRD3) expression in rat spinal cord was determined using RT-qPCR. The mechanical, thermal, and cold responses in animals were assessed at the indicated time after surgery. The levels of inflammatory cytokines in rat spinal cord were measured by ELISA. The changes in NF-κB signaling-related molecules in rat spinal cord were determined using western blot and immunofluorescence. MiR-200a-3p was underexpressed in CCI rats in a time-dependent manner. Overexpression of miR-200a-3p decreased mechanical hyperalgesia and thermal sensitivity to attenuate neuropathic pain in rats. BRD3 was targeted by miR-200a-3p. Additionally, downregulation of BRD3 inhibited neuropathic pain progression. Moreover, overexpression of BRD3 rescued the effect of miR-200a-3p on NF-κB signaling and neuropathic pain in CCI rats. MiR-200a-3p attenuates neuropathic pain via downregulating BRD3 to block NF-κB signaling.
期刊介绍:
The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.